Premium
INHIBITION OF ARACHIDONIC ACID RELEASE AS THE MECHANISM BY WHICH GLUCOCORTICOIDS INHIBIT ENDOTOXIN‐INDUCED DIARRHOEA
Author(s) -
DOHERTY NIALL S.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb10454.x
Subject(s) - arachidonic acid , mechanism (biology) , glucocorticoid , chemistry , pharmacology , endocrinology , medicine , biochemistry , enzyme , philosophy , epistemology
1 Dexamethasone blocked endotoxin‐induced diarrhoea in mice, but not that induced by arachidonic acid or prostaglandin E 2 . 2 Indomethacin blocked endotoxin and arachidonic acid‐induced diarrhoea, but not that induced by prostaglandin E 2 . 3 Codeine blocked all three forms of diarrhoea. 4 The above data, when considered in relation to literature reports that endotoxin induces prostaglandin synthesis, suggest that dexamethasone blocks diarrhoea by preventing the release of arachidonic acid, the substrate for prostaglandin biosynthesis. 5 The activities of indomethacin and dexamethasone in castor oil diarrhoea support the above conclusion and their inactivity in 5‐hydroxytryptophan‐induced diarrhoea confirms the absence of ‘codeine‐like’ direct effects on the gut. 6 Other glucocorticoids (hydrocortisone, prednisolone) were also able to block endotoxin diarrhoea, but oestradiol, testosterone and progesterone did not. 7 The inhibitory action of dexamethasone on endotoxin diarrhoea could not be blocked by the protein synthesis inhibitor, cycloheximide, nor by the glucocorticoid receptor antagonist, progesterone. Thus, involvement of glucocorticoid receptor‐mediated gene activation could not be demonstrated.